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test the safety and efficacy of this new formulation in young children

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Bringing antiretroviral drugs to children

The CHAPAS trials have ensured that many more children with HIV have benefited
from life-saving antiretrovirals.

The challenge

Leishmania infections of body tissues (visceral leishmaniasis or kala azar) can be fatal if untreated. East Africa is particularly badly affected by visceral leishmaniasis, and up to 70% of infections occur in children.

Treatment of visceral leishmaniasis has typically relied on drugs that have unpleasant side effects and are difficult to administer, requiring daily injections for 17 days. Diagnosis is also difficult, and some methods are associated with a significant risk of harm.

The AfriKADIA project aims to improve management of visceral leishmaniasis, by developing safer and easier to administer treatments and by evaluating new tools for rapid diagnosis of infections. It has a particular focus on approaches that are suitable for the remote rural populations characteristic of affected East African countries.

The project is developing a combination therapy, based on miltefosine and paromomycin, that can be given orally and is suitable for use in remote settings with limited access to healthcare facilities.  Following studies of the metabolism of this combination in patients, it will be tested in a large phase III trial comparing its safety and efficacy with the standard 17-day treatment. 

The project will also evaluate possible tests to determine whether patients have been cured or are at risk or relapse, as well as rapid point-of-care tests for detecting new infections.

The project

The later CHAPAS-3 trial compared the efficacy and safety of three fixed-dose combinations including two without stavudine (found to have some long-term side effects in adults, leading to a recommendation that its use be discontinued in children). The trial the first of its kind in Africa studied nearly 500 children at four sites in two African countries.

The AfriKADIA project will generate key evidence on the efficacy of the miltefosine and paromomycin combination, to inform decision-making on its introduction in East Africa. In addition, it will identify tools that could be adopted to improve control of visceral leishmaniasis and ultimately drive forward elimination of the disease in the region.

ratios forfixed-dose combinations and on appropriatedosage according to weight. 

The CHAPAS-3 trial confirmed the effectiveness of fixed-dose combinations, providing further impetus to the rollout of antiretrovirals to children. Its evidence on abacavir informed the WHO recommendation of abacavir-containing combinations for first-line therapy in children. Trial data have also been used to support applications for regulatory approval for new scored efavirenz tablets.

Impact